Characteristics of a new meningococcal serogroup B vaccine, bivalent rLP2086 (MenB-FHbp; Trumenba®)

Figures & data

Figure 1. Serogroup B vaccine development. Serogroup B vaccine development has focused on surface proteins that elicit a sufficient immune response, are present in a majority of MnB disease strains, and have limited immunologic variability across diverse serogroup B strains. A conserved surface-exposed bacterial lipoprotein and human complement fHBP, also known as LP2086, was identified as a promising vaccine target.

fHBP: factor H binding protein; MnB: meningococcal serogroup B.

Figure 2. Meningococcal serogroup B factor H binding protein. MnB strains contain 1 of 2 distinct protein subfamilies of fHBP: subfamily A and subfamily B. Other groups also categorize fHBP into three variants (i.e. 1, 2, and 3) or 9 modular groups (i.e. I to IX).

fHBP: factor H binding protein; MnB: meningococcal serogroup B.

Figure 3. Role of factor H binding protein in immune response. (a) Meningococci recruit hFH to the cell surface; hFH binds fHBP, preventing complement from binding and allowing the bacterium to escape destruction by the innate immune system. (b) fHBP-specific antibodies, such as bivalent rLP2086 meningococcal B vaccine, prevent hFH from binding to fHBP, allowing complement to be deposited on the surface of the bacterium via direct binding to the pathogen (alternative pathway) or fixed to antibodies on the pathogen surface (classical pathway). Antibodies targeting fHBP can kill serogroup B meningococci via direct lysis or through phagocytosis.

fH: factor H; fHBP: factor H binding protein; hFH: human factor H.

Figure 4. Serum bactericidal assay with 4 different test strains of serogroup B N meningitidis used in bivalent rLP2086 studies.

fHBP: factor H binding protein; MnB: meningococcal serogroup B.

Table 1. Summary of phase 2 studies of bivalent rLP2086 meningococcal B vaccine in adolescents.

Study	Study description	Study population	hSBA ≥LLOQ 1 month after third dose, % of subjects
Vesikari et al. [77]	Single-blind, placebo-controlled dosing study	Healthy adolescents aged 11–18 years (N = 1713)	95–99% for subfamily A strains
			86–89% for subfamily B strains
Vesikari et al. [76]	Randomized, placebo-controlled study of dTaP-inactivated polio vaccine + bivalent rLP2086 vaccine or saline	Healthy adolescents aged 11–18 years (N = 749)	Bivalent rLP2086 + dTaP:
			96–100% for subfamily A strains
			82–97% for subfamily B strains
Senders et al. [75]	Observer-blinded, randomized study of coadministration of HPV4 vaccine with bivalent rLP2086 vaccine	Healthy male or female adolescents aged 11–<18 years (N = 2499)	Bivalent rLP2086 + HPV4:
			94–99% for subfamily A strains
			83–91% for subfamily B strains
			Bivalent rLP2086 + saline:
			96–99% for subfamily A strains
			86–93% for subfamily B strains
Muse et al. [74]	Phase 2, randomized, active-controlled, observer-blinded, multicenter study of coadministration of MCV4, dTaP, and bivalent rLP2086	Healthy male or female adolescents aged 10–<13 years (N = 2628)	Bivalent rLP2086 + MCV4 + dTaP:
			88% for subfamily A strain
			90% for subfamily B strain
			Bivalent rLP2086 + saline:
			91% for subfamily A strain
			93% for subfamily B strain

dTaP: diphtheria, tetanus, and pertussis; hSBA: serum bactericidal assay using human complement; HPV: human papilloma virus; LLOQ: lower limit of quantification; MCV4: quadrivalent A, C, W, Y meningococcal conjugate vaccine.

LLOQ = ≥ 1:8 for A56, B24, B44; ≥1:16 for A22.

Vesikari T, Østergaard L, Diez-Domingo J, et al. Meningococcal serogroup B bivalent rLP2086 vaccine elicits broad and robust serum bactericidal responses in healthy adolescents. J Pediatric Infect Dis Soc. 2016 Jun;5(2):152–160.

 PubMed Web of Science ®Google Scholar

Vesikari T, Wysocki J, Beeslaar J, et al. Immunogenicity, safety, and tolerability of bivalent rLP2086 meningococcal group B vaccine administered concomitantly with diphtheria, tetanus, and acellular pertussis and inactivated poliomyelitis vaccines to healthy adolescents. J Pediatric Infect Dis Soc. 2016 Jun;5(2):180–187.

 PubMed Web of Science ®Google Scholar

Senders S, Bhuyan P, Jiang Q, et al. Immunogenicity, tolerability, and safety in adolescents of bivalent rLP2086, a meningococcal serogroup B vaccine, coadministered with quadrivalent human papilloma virus vaccine. Pediatr Infect Dis J. 2016;35:548–554.

 PubMed Web of Science ®Google Scholar

Muse D, Christensen S, Bhuyan P, et al. A phase 2, randomized, active-controlled, observer-blinded study to assess the immunogenicity, tolerability, and safety of bivalent rLP2086, a meningococcal serogroup B vaccine, coadministered with tetanus, diphtheria and acellular pertussis vaccine and serogroup A, C, Y and W-135 meningococcal conjugate vaccine in healthy US adolescents. Pediatr Infect Dis J. 2016 Jun;35(6):673–682.

 PubMed Web of Science ®Google Scholar